阅读说明：本技术 一种3，4-吡啶二酰亚胺类衍生物的制备方法 (Preparation method of 3, 4-pyridine diimides derivatives ) 是由 罗海清 李小兰 范莉莉 于 2021-07-22 设计创作，主要内容包括：本发明提供一种3,4-吡啶二酰亚胺类衍生物的制备方法,属于有机合成技术领域。本发明提供的3,4-吡啶二酰亚胺类衍生物的方法具有操作简单,原子经济性高,底物范围广,官能团耐受性好等优点。该类化合物同时含吡啶和马来酰亚胺两种重要的核心有用骨架,对于活性药物分子和功能材料的研发具有重要价值。(The invention provides a preparation method of a 3, 4-pyridine diimides derivative, belonging to the technical field of organic synthesis. The method for preparing the 3, 4-pyridine diimides derivatives has the advantages of simple operation, high atom economy, wide substrate range, good functional group tolerance and the like. The compound simultaneously contains two important core useful skeletons of pyridine and maleimide, and has important value for the research and development of active drug molecules and functional materials.)

1. A3, 4-pyridine diimides derivative is characterized by having a structure shown as a formula I:

wherein R is¹Hydrogen, fluorine, chlorine, phenyl, alkyl, alkoxy, iodine, bromine, trifluoromethyl; r²Is hydrogen, alkyl or aryl; r³Is methyl or ethyl.

2. A 3, 4-pyridinebisimide derivative according to claim 1, wherein said 3, 4-pyridinebisimide derivative comprises:

3. the process for preparing 3, 4-pyridinebisimide derivatives according to claim 1 or 2, comprising the steps of:

mixing enamide, maleimide and an accelerator A with a solvent, and carrying out a [ 4+2 ] cyclization reaction to obtain a 3, 4-pyridine diimide derivative;

wherein the enamide has a structure represented by formula II:

the maleimide has a structure represented by formula III:

4. the method for preparing 3, 4-pyridinediimides derivative according to claim 3, characterized in that the cyclization reaction is carried out in an oil bath, the temperature of the oil bath is 80-140 ℃, and the time of the cyclization reaction is 12-36 h.

5. The method for preparing 3, 4-pyridinebisimide derivatives according to claim 3, characterized in that the solvent is DMF, DMSO, PhCl, THF, DCE, Dioxane, EtOH, DMF/DMSO (1:1) or DMF/PhCl (1:1), and the volume of the solvent is 1.0mL-4.0 mL.

6. The method for preparing 3, 4-pyridinediimides derivative according to claim 3, characterized in that the promoter A is copper sulfate, copper chloride, cuprous oxide, ferric chloride, aluminum chloride, copper acetate, manganese carbonate, manganese chloride, manganese sulfate, nickel acetate, silver acetate, boron trifluoride etherate, acetic acid, Lewis acid or protonic acid.

7. The process for preparing 3, 4-pyridinebisimide derivatives as claimed in claim 4, wherein the temperature of the cyclization reaction is 120 ℃ and the time is 24 h.

8. The method for preparing 3, 4-pyridinediimides derivative according to claim 5, wherein the solvent is DMF/PhCl ═ 1:1(2.0 mL).

9. The method for preparing 3, 4-pyridinebisimide derivatives as claimed in claim 3, wherein the molar ratio of the enamide, the maleimide and the accelerator A is 1.0 (2.0-4.0) to (0.1-1.0).

10. The method for preparing 3, 4-pyridinediimides derivative according to claim 6, characterized in that alkene amide and maleimide compound are used as reaction substrates, and the mixture is mixed with solvent and then is promoted by Lewis acid or protonic acid to produce 3, 4-pyridinediimides derivative.

Technical Field

One or more embodiments of the present disclosure relate to the field of organic synthesis technology, and in particular, to a method for preparing a 3, 4-pyridinebisimide derivative.

Background

Organic matters containing pyridine skeleton and maleimide skeleton are two important nitrogen heterocyclic compounds, and are widely present in natural products, active medicines and functional materials. For example, diprolidine (bicyclic pyridine) and nakinadine (norepinephrine a) are two structurally diverse natural products containing a pyridine core. The pyridine-derived drugs can be used for Human Immunodeficiency Virus (HIV) and chronic myeloid leukemia. Pyridine derivatives are also added to polymers, such as polyvinylpyridine (PVP). The development of methods for synthesizing pyridine has received a great deal of attention from chemists.

The maleimide skeleton-containing compound has good biological activity, fluorescence property and the like, and a series of reported bis-indole maleimide compounds are used for OLED materials (chem. Mater.2006, 18, 832; J.Mat. chem.2009, 19, 5141; J.Photochem.Photobiol.A2007, 192, 8).

Although many techniques for synthesizing pyridine derivatives, such as transition metal catalyzed synthesis of pyridine derivatives or metal-free reaction to obtain pyridine derivatives, have been reported, these methods have achieved remarkable success, but no method for constructing pyridine structure by using enamide and maleimide has been reported, so that the method for synthesizing 3, 4-pyridinediimides derivatives by promoting [ 4+2 ] cyclization of enamide and maleimide by lewis acid would be extremely innovative and practical, and the synthesized product contains two useful framework units, namely pyridine and maleimide.

Disclosure of Invention

In view of the above, one or more embodiments of the present disclosure are directed to a method for preparing a 3, 4-pyridinebisimide derivative, which solves the problems set forth in the background art.

In view of the above, one or more embodiments of the present disclosure provide a 3, 4-pyridine diimide derivative having a structure represented by formula I:

wherein R is¹Hydrogen, fluorine, chlorine, phenyl, alkyl, alkoxy, iodine, bromine, trifluoromethyl; r²Is hydrogen, alkyl or aryl; r³Is methyl or ethyl.

Preferably, the 3, 4-pyridinebisimide derivative comprises:

a preparation method of 3, 4-pyridine diimides derivatives comprises the following steps:

mixing enamide, maleimide and an accelerator A with a solvent, and carrying out a [ 4+2 ] cyclization reaction to obtain a 3, 4-pyridine diimide derivative;

wherein the enamide has a structure represented by formula II:

the maleimide has a structure represented by formula III:

more preferably, the cyclization reaction is carried out under the condition of an oil bath, the temperature of the oil bath is 80-140 ℃, and the time of the cyclization reaction is 12-36 h.

More preferably, the solvent is DMF, DMSO, PhCl, THF, DCE, Dioxane, EtOH, DMF/DMSO (1:1) or DMF/PhCl (1:1), and the volume of the solvent is 1.0mL to 4.0 mL.

More preferably, the accelerant A is copper sulfate, copper chloride, cuprous oxide, ferric chloride, aluminum chloride, copper acetate, manganese carbonate, manganese chloride, manganese sulfate, nickel acetate, silver acetate, boron trifluoride diethyl etherate, acetic acid, Lewis acid or protonic acid.

More preferably, the temperature of the cyclization reaction is 120 ℃ and the time is 24 h.

More preferably, the solvent is DMF/PhCl ═ 1:1(2.0 mL).

More preferably, the mol ratio of the alkene amide, the maleimide and the accelerator A is 1.0 (2.0-4.0) to 0.1-1.0.

More preferably, the 3, 4-pyridinediimides derivatives are produced by mixing an enamide and a maleimide compound as reaction substrates with a solvent and then accelerating the reaction by a Lewis acid or a protonic acid.

From the above, it can be seen that the beneficial effects of the present invention are: the invention provides a method for synthesizing 3, 4-pyridine diimides derivatives, which has the advantages of simple operation, high atom economy, wide substrate range, good functional group tolerance and the like, and has important value for the research and development of active drug molecules and functional materials.

Drawings

In order to more clearly illustrate one or more embodiments or prior art solutions of the present specification, the drawings that are needed in the description of the embodiments or prior art will be briefly described below, and it is obvious that the drawings in the following description are only one or more embodiments of the present specification, and that other drawings may be obtained by those skilled in the art without inventive effort from these drawings.

FIGS. 1-2 are nuclear magnetic hydrogen spectra and carbon praseodymium plots of a product prepared according to a first example of the present invention;

FIGS. 3-4 are nuclear magnetic hydrogen spectra and carbon praseodymium plots of the product prepared in example two of the present invention;

5-6 are nuclear magnetic hydrogen spectra and carbon spectra of the product prepared in example III of the present invention;

FIGS. 7-8 are nuclear magnetic hydrogen spectra and carbon praseodymium plots of the product of example four of the present invention;

FIGS. 9-10 are nuclear magnetic hydrogen spectra and carbon praseodymium plots of the product prepared in example five of the present invention;

FIGS. 11-12 are nuclear magnetic hydrogen and carbon spectra of a product prepared according to example VI of the present invention;

FIGS. 13-14 are nuclear magnetic hydrogen spectra and carbon praseodymium plots of the product prepared in example seven of the present invention;

FIGS. 15-16 are nuclear magnetic hydrogen spectra and carbon praseodymium plots of the product prepared in example eight of the present invention;

FIGS. 17-18 are nuclear magnetic hydrogen and carbon spectra of a product prepared according to example nine of the present invention;

FIGS. 19-20 are nuclear magnetic hydrogen spectra and carbon praseodymium plots of the product prepared in example ten of the present invention;

FIGS. 21-22 are nuclear magnetic hydrogen spectra and carbon praseodymium plots of a product prepared in example eleven of the present invention;

FIGS. 23-24 are nuclear magnetic hydrogen and carbon spectra of a product prepared in example twelve of the present invention;

FIGS. 25-26 are nuclear magnetic hydrogen spectra and carbon praseodymium plots of products prepared in example thirteen of the present invention;

FIGS. 27-28 are nuclear magnetic hydrogen and carbon spectra of a product prepared according to example fourteen of the present invention;

29-30 are nuclear magnetic hydrogen spectra and carbon praseodymium plots of products prepared by example fifteen of the present invention;

FIGS. 31-32 are nuclear magnetic hydrogen spectra and carbon praseodymium plots of the product of example sixteen of the present invention;

FIGS. 33-34 are nuclear magnetic hydrogen and carbon spectra of a product prepared according to seventeen example of the present invention;

FIGS. 35-36 are nuclear magnetic hydrogen spectra and carbon praseodymium plots of the product of example eighteen of the invention;

fig. 37-38 are nuclear magnetic hydrogen and carbon spectra of the product prepared in nineteen examples of the invention.

Detailed Description

To make the objects, technical solutions and advantages of the present disclosure more apparent, the present disclosure is further described in detail below with reference to specific embodiments.

One or more embodiments of the present disclosure provide a 3, 4-pyridine diimide derivative having a structure represented by formula I:

wherein R is¹Hydrogen, fluorine, chlorine, phenyl, alkyl, alkoxy, iodine, bromine, trifluoromethyl; r²Is hydrogen, alkyl or aryl; r³Is methyl or ethyl.

As a modification of the above scheme, the 3, 4-pyridinebisimide derivatives include:

a preparation method of 3, 4-pyridine diimides derivatives comprises the following steps:

mixing enamide, maleimide and an accelerator A with a solvent, and carrying out a [ 4+2 ] cyclization reaction to obtain a 3, 4-pyridine diimide derivative;

wherein the enamide has a structure represented by formula II:

the maleimide has a structure represented by formula III:

as a modification of the scheme, the cyclization reaction is carried out under the condition of an oil bath, the temperature of the oil bath is 80-140 ℃, and the time of the cyclization reaction is 12-36 h.

As a modification of the above, the solvent is DMF, DMSO, PhCl, THF, DCE, Dioxane, EtOH, DMF/DMSO (1:1) or DMF/PhCl (1:1), and the volume of the solvent is 1.0mL to 4.0 mL.

As a modification of the scheme, the accelerant A is copper sulfate, copper chloride, cuprous oxide, ferric chloride, aluminum chloride, copper acetate, manganese carbonate, manganese chloride, manganese sulfate, nickel acetate, silver acetate, boron trifluoride diethyl etherate, acetic acid, Lewis acid or protonic acid.

As a modification of the above, the temperature of the cyclization reaction is 120 ℃ and the time is 24 h.

As a modification of the above, the solvent is DMF/PhCl ═ 1:1(2.0 mL).

As a modified scheme of the scheme, the mol ratio of the enamide, the maleimide and the accelerator A is 1.0 (2.0-4.0) to 0.1-1.0.

As an improvement scheme of the scheme, the alkene amide and the maleimide compound are used as reaction substrates, and are mixed with a solvent to generate the 3, 4-pyridine diimides derivatives under the accelerating action of Lewis acid or protonic acid.

In the present invention, the preparation process of the pyridine derivative is as follows:

the preparation method is not particularly limited in conditions of the preparation process of the pyridine derivative, and in the embodiment of the invention, the enamide and the maleimide are dissolved in a DMF/PhCl mixed solvent, an accelerant is added at room temperature for reaction, and after the reaction is finished, the pyridine derivative is obtained by extraction, concentration and separation.

Example one

Preparation of 2, 4-dimethyl-6-phenyl-1H-pyrrolo [3,4-c ] pyridine 1,3(2H) -dione:

n- (1-phenylvinyl) acetamide (48.4mg, 0.3mmol), N-methylmaleimide (102.0mg, 0.9mmol), promoter manganese acetate (26.5mg, 0.15mmol) were weighed out, 2mL of a mixed solvent (DMF/PhCl ═ 1:1) was added thereto, and the mixture was reacted in an oil bath at 120 ℃ for 24 hours, after completion of the reaction, extracted with 20.0mL × 3 of ethyl acetate, the organic phases were combined, dried over anhydrous sodium sulfate, and separated by column chromatography (eluent: petroleum ether/ethyl acetate ═ 50:1) to obtain the desired product 2, 4-dimethyl-6-phenyl-1H-pyrrolo [3,4-c ] pyridine 1,3(2H) -dione (53.7mg, white solid, 71% yield).

Performing nuclear magnetic hydrogen spectrum and nuclear magnetic carbon spectrum characterization on the product prepared in the first embodiment, wherein specific spectrograms are shown in figures 1-2, and specific data are as follows:

¹H NMR(400MHz,CDCl₃)δ8.14–8.08(m,2H),7.99(s,1H),7.51(dd,J＝5.6,1.8Hz,3H),3.20(s,3H),2.95(s,3H)；¹³C NMR(101MHz,CDCl₃)δ168.2,167.1,162.4,156.6,141.4,137.7,130.6,129.0,127.5,121.0,111.1,24.0,21.3.

example two

Preparation of 2, 4-dimethyl-6- (p-tolyl) -1H-pyrrolo [3,4-c ] pyridine 1,3(2H) -dione:

n- (1- (p-tolyl) vinyl) acetamide (52.6mg, 0.3mmol), N-methylmaleimide (102.0mg, 0.9mmol), a promoter manganese acetate (26.5mg, 0.15mmol) were weighed out, and 2mL of a mixed solvent (DMF/PhCl ═ 1:1) was added thereto, and the mixture was reacted in an oil bath at 120 ℃ for 24 hours, after completion of the reaction, extraction was performed with 20.0mL × 3 of ethyl acetate, the organic phases were combined, dried over anhydrous sodium sulfate, and separated by column chromatography (eluent: petroleum ether/ethyl acetate ═ 50:1) to obtain the objective 2, 4-dimethyl-6- (p-tolyl) -1H-pyrrolo [3,4-c ] pyridine 1,3(2H) -dione (51.6 mg, white solid, 65% yield).

Performing nuclear magnetic hydrogen spectrum and nuclear magnetic carbon spectrum characterization on the product prepared in the second embodiment, wherein specific spectrograms are shown in fig. 3-4, and specific data are as follows:

¹H NMR(400MHz,CDCl₃)δ7.96(d,J＝8.2Hz,2H),7.89(s,1H),7.27(d,J＝7.8Hz,2H),3.15(s,3H),2.89(s,3H),2.40(s,3H)；¹³C NMR(101MHz,CDCl₃)δ168.2,167.1,162.2,156.5,141.2,140.9,134.8,129.6,127.3,120.5,110.6,24.0,21.3,21.3.

EXAMPLE III

Preparation of 6- (4-methoxyphenyl) -2, 4-dimethyl-1H-pyrrolo [3,4c ] pyridine-1, 3(2H) -dione:

n- (1- (4-methoxyphenyl) vinyl) acetamide (57.3mg, 0.3mmol), N-methylmaleimide (102.0mg, 0.9mmol), a promoter manganese acetate (26.5mg, 0.15mmol) were weighed out, 2mL of a mixed solvent (DMF/PhCl ═ 1:1) was added thereto, and the mixture was reacted in an oil bath at 120 ℃ for 24 hours, after completion of the reaction, extraction was performed with 20.0mL × 3 of ethyl acetate, and the organic phases were combined, dried over anhydrous sodium sulfate, and separated by column chromatography (eluent: petroleum ether/ethyl acetate ═ 50:1) to obtain the objective product 6- (4-methoxyphenyl) -2, 4-dimethyl-1H-pyrrolo [3,4c ] pyridine-1, 3(2H) -dione 71.7mg, a pale yellow solid, with a yield of 85%.

Performing nuclear magnetic hydrogen spectrum and nuclear magnetic carbon spectrum characterization on the product prepared in the third embodiment, wherein specific spectrograms are shown in fig. 5-6, and specific data are as follows:

¹H NMR(400MHz,CDCl₃)δ8.19–7.96(m,2H),7.86(s,1H),6.98(d,J＝8.9Hz,2H),3.86(s,3H),3.16(s,3H),2.89(s,3H)；¹³C NMR(101MHz,CDCl₃)δ168.3,167.2,161.8,161.8,156.5,141.2,130.2,129.0,120.0,114.3,110.1,55.4,24.0,21.3.

example four

Preparation of 6- (4-fluorophenyl) -2, 4-dimethyl-1H-pyrrolo [3,4-c ] pyridine-1, 3(2H) -dione:

n- (1- (4-fluorophenyl) vinyl) acetamide (53.7mg, 0.3mmol), N-methylmaleimide (102.0mg, 0.9mmol), a promoter manganese acetate (26.5mg, 0.15mmol) were weighed out, 2mL of a mixed solvent (DMF/PhCl ═ 1:1) was added thereto, and the mixture was reacted in an oil bath at 120 ℃ for 24 hours, after completion of the reaction, extraction was performed with 20.0mL × 3 of ethyl acetate, the organic phases were combined, dried over anhydrous sodium sulfate, and separated by column chromatography (eluent: petroleum ether/ethyl acetate ═ 50:1) to obtain the objective product 6- (4-fluorophenyl) -2, 4-dimethyl-1H-pyrrolo [3,4-c ] pyridine-1, 3(2H) -dione 42.0mg, white solid, yield 52%.

And performing nuclear magnetic hydrogen spectrum and nuclear magnetic carbon spectrum characterization on the product prepared in the fourth embodiment, wherein specific spectrograms are shown in fig. 7-8, and specific data are as follows:

¹HNMR(400MHz,CDCl₃)δ8.16–8.05(m,2H),7.92(s,1H),7.23–7.14(m,2H),3.18(s,3H),2.92(s,3H)；¹³C NMR(101MHz,CDCl₃)δ168.2,167.0,164.4(d,¹J_C-F＝251.6Hz),161.2,156.7,141.5,133.9(d,⁴J_C-F＝3.0Hz),129.6(d,³J_C-F＝8.8Hz),120.9,116.0(d,²J_C-F＝21.7Hz),110.7,24.1,21.3.

EXAMPLE five

Preparation of (4-chlorophenyl) -2, 4-dimethyl-1H-pyrrolo [3,4-c ] pyridine-1, 3(2H) -dione:

n- (1- (4-chlorophenyl) vinyl) acetamide (58.7mg, 0.3mmol), N-methylmaleimide (102.0mg, 0.9mmol), a promoter manganese acetate (26.5mg, 0.15mmol) were weighed out, and 2mL of a mixed solvent (DMF/PhCl ═ 1:1) was added thereto, and the mixture was reacted in an oil bath at 120 ℃ for 24 hours, after completion of the reaction, extracted with 20.0mL × 3 of ethyl acetate, the organic phases were combined, dried over anhydrous sodium sulfate, and separated by column chromatography (eluent: petroleum ether/ethyl acetate ═ 50:1) to obtain the objective 6- (4-chlorophenyl) -2, 4-dimethyl-1H-pyrrolo [3,4-c ] pyridine-1, 3(2H) -dione (44.2 mg, white solid, yield 51%).

Performing nuclear magnetic hydrogen spectrum and nuclear magnetic carbon spectrum characterization on the product prepared in the fifth embodiment, wherein specific spectrograms are shown in fig. 9-10, and specific data are as follows:

¹H NMR(400MHz,CDCl₃)δ8.07–7.99(m,2H),7.91(s,1H),7.49–7.40(m,2H),3.18(s,3H),2.91(s,3H)；¹³C NMR(101MHz,CDCl₃)δ168.1,166.9,161.0,156.7,141.5,136.9,136.0,129.2,128.7,121.2,110.8,24.1,21.3.

EXAMPLE six

Preparation of 2, 4-dimethyl-6- (4- (trifluoromethyl) phenyl) -1H-pyrrolo [3,4-c ] pyridine-1, 3(2H) -dione:

n- (1- (4- (trifluoromethyl) phenyl) vinyl) acetamide (68.8mg, 0.3mmol), N-methylmaleimide (102.0mg, 0.9mmol), a promoter manganese acetate (26.5mg, 0.15mmol) were weighed out, and 2mL of a mixed solvent (DMF/PhCl ═ 1:1) was added thereto, and reacted in an oil bath at 120 ℃ for 24 hours, after completion of the reaction, the reaction product was extracted with 20.0mL × 3 of ethyl acetate, the organic phases were combined, dried over anhydrous sodium sulfate, and separated by column chromatography (eluent: petroleum ether/ethyl acetate ═ 50:1) to obtain the objective product 2, 4-dimethyl-6- (4- (trifluoromethyl) phenyl) -1H-pyrrolo [3,4-c ] pyridine-1, 3(2H) -dione (39.3 mg, white solid, yield 41%).

Performing nuclear magnetic hydrogen spectrum and nuclear magnetic carbon spectrum characterization on the product prepared in the sixth embodiment, wherein specific spectrograms are shown in fig. 11-12, and specific data are as follows:

¹H NMR(400MHz,CDCl₃)δ8.28–8.15(m,2H),8.01(s,1H),7.85–7.64(m,2H),3.20(s,3H),2.96(s,3H)；¹³C NMR(101MHz,CDCl₃)δ168.0,166.8,160.7,157.0,141.7,140.9(d,⁴J_C-F＝1.2Hz),132.2(q,²J_C-F＝32.6Hz),127.9,125.9(q,³J_C-F＝3.8Hz),123.9(d,¹J_C-F＝272.4Hz),121.9,111.4,24.2,21.3.

EXAMPLE seven

Preparation of 6- (4-bromophenyl) -2, 4-dimethyl-1H-pyrrolo [3,4-c ] pyridine-1, 3(2H) -dione:

n- (1- (4-bromophenyl) vinyl) acetamide (72.0mg, 0.3mmol), N-methylmaleimide (102.0mg, 0.9mmol), a promoter manganese acetate (26.5mg, 0.15mmol) were weighed out, and 2mL of a mixed solvent (DMF/PhCl ═ 1:1) was added thereto, and the mixture was reacted in an oil bath at 120 ℃ for 24 hours, after completion of the reaction, extraction was performed with 20.0mL × 3 of ethyl acetate, and the organic phases were combined, dried over anhydrous sodium sulfate, and separated by column chromatography (eluent: petroleum ether/ethyl acetate ═ 50:1) to obtain the objective product 6- (4-bromophenyl) -2, 4-dimethyl-1H-pyrrolo [3,4-c ] pyridine-1, 3(2H) -dione in 56.5mg of a pale yellow solid with a yield of 57%.

Performing nuclear magnetic hydrogen spectrum and nuclear magnetic carbon spectrum characterization on the product prepared in the seventh embodiment, wherein specific spectrograms are shown in fig. 13-14, and specific data are as follows:

¹H NMR(400MHz,CDCl₃)δ7.96(d,J＝8.6Hz,2H),7.92(s,1H),7.61(d,J＝8.6Hz,2H),3.18(s,3H),2.92(s,3H)；¹³C NMR(101MHz,CDCl₃)δ168.1,166.9,161.0,156.8,141.5,136.5,132.2,129.0,125.4,121.3,110.8,24.1,21.3.

example eight

Preparation of 6- (4-iodophenyl) -2, 4-dimethyl-1H-pyrrolo [3,4-c ] pyridine-1, 3(2H) -dione:

n- (1- (4-iodophenyl) vinyl) acetamide (86.1mg, 0.3mmol), N-methylmaleimide (102.0mg, 0.9mmol), promoter manganese acetate (26.5mg, 0.15mmol) were weighed out, 2mL of a mixed solvent (DMF/PhCl ═ 1:1) was added thereto, and the mixture was reacted in an oil bath at 120 ℃ for 24 hours, after completion of the reaction, extraction was performed with 20.0mL × 3 of ethyl acetate, and the organic phases were combined, dried over anhydrous sodium sulfate, and separated by column chromatography (eluent: petroleum ether/ethyl acetate ═ 50:1) to obtain the objective product 6- (4-iodophenyl) -2, 4-dimethyl-1H-pyrrolo [3,4-c ] pyridine-1, 3(2H) -dione, 70.1mg of a white solid, with a yield of 62%.

Performing nuclear magnetic hydrogen spectrum and nuclear magnetic carbon spectrum characterization on the product prepared in the example VIII, wherein specific spectrograms are shown in the figures 15-16, and specific data are as follows:

¹HNMR(400MHz,CDCl₃)δ7.93(s,1H),7.83(s,4H),3.19(s,3H),2.92(s,3H)；¹³C NMR(101MHz,CDCl₃)δ168.1,166.9,161.2,156.8,141.5,138.2,137.1,129.0,121.4,110.8,97.6,24.1,21.3.

example nine

Preparation of 6- ([1,1' -biphenyl ] -4-yl) -2, 4-dimethyl-1H-pyrrolo [3,4-c ] pyridine-1, 3(2H) -dione:

weighing N- (1- ([1,1 '-biphenyl ] -4-yl) vinyl) acetamide (71.2mg, 0.3mmol), N-methylmaleimide (102.0mg, 0.9mmol) and promoter manganese acetate (26.5mg, 0.15mmol), adding mixed solvent 2mL (DMF/PhCl ═ 1:1), reacting in an oil bath kettle at 120 ℃ for 24 hours, extracting with 20.0mL × 3 ethyl acetate, combining organic phases, drying with anhydrous sodium sulfate, separating by column chromatography (eluent: petroleum ether/ethyl acetate ═ 50:1) to obtain target product 6- ([1,1' -biphenyl ] -4-yl) -2, 4-dimethyl-1H-pyrrolo [3,4-c ] pyridine-1, 3(2H) -dione (62.1 mg), pale yellow solid, yield 63%.

And performing nuclear magnetic hydrogen spectrum and nuclear magnetic carbon spectrum characterization on the product prepared in the ninth embodiment, wherein specific spectrograms are shown in fig. 17-18, and specific data are as follows:

¹H NMR(400MHz,CDCl₃)δ8.22–8.16(m,2H),8.02(s,1H),7.77–7.71(m,2H),7.68–7.62(m,2H),7.51–7.45(m,2H),7.42–7.36(m,1H),3.19(s,3H),2.96(s,3H)；¹³C NMR(101MHz,CDCl₃)δ168.3,167.2,162.0,156.7,143.3,141.4,140.0,136.6,128.9,128.0,127.9,127.6,127.1,120.9,111.0,24.1,21.4.

example ten

Preparation of 2, 11-dimethyl-4, 5-dihydro-1H-benzo [ H ] pyrrolo [3,4-c ] quinoline-1, 3(2H) -dione:

n- (3, 4-dihydronaphthalen-1-yl) acetamide (56.2mg, 0.3mmol), N-methylmaleimide (102.0mg, 0.9mmol), promoter manganese acetate (26.5mg, 0.15mmol) were weighed, 2mL of a mixed solvent (DMF/PhCl ═ 1:1) was added thereto, and reacted in an oil bath at 120 ℃ for 24 hours, after completion of the reaction, extracted with 20.0mL × 3 of ethyl acetate, the organic phases were combined, dried over anhydrous sodium sulfate, and separated by column chromatography (eluent: petroleum ether/ethyl acetate ═ 50:1) to obtain the objective product 2, 11-dimethyl-4, 5-dihydro-1H-benzo [ H ] pyrrolo [3,4-c ] quinoline-1, 3(2H) -dione (37.4 mg, yellow solid, yield 45%).

Performing nuclear magnetic hydrogen spectrum and nuclear magnetic carbon spectrum characterization on the product prepared in the example ten, wherein specific spectrograms are shown in figures 19-20, and specific data are as follows:

¹HNMR(400MHz,CDCl₃)δ8.31(dd,J＝7.3,1.9Hz,1H),7.34(m,2H),7.22(dd,J＝7.0,1.8Hz,1H),3.43–3.36(t,2H),3.12(s,3H),2.93(t,2H),2.85(s,3H)；¹³C NMR(101MHz,CDCl₃)δ168.0,167.9,158.1,154.1,138.9,135.6,133.0,130.7,128.0,127.2,127.2,126.1,120.8,26.8,23.8,22.1,21.0.

EXAMPLE eleven

Preparation of 2, 11-dimethyltryptophanyl [4,3-b ] pyrrolo [3,4-d ] pyridine-1, 3(2H,4H) -dione:

n- (2H-benzofuran-4-yl) acetamide (56.8mg, 0.3mmol), N-methylmaleimide (102.0mg, 0.9mmol), promoter manganese acetate (26.5mg, 0.15mmol) were weighed out, 2mL of a mixed solvent (DMF/PhCl ═ 1:1) was added thereto, and the mixture was reacted in an oil bath at 120 ℃ for 24 hours, after completion of the reaction, extraction was performed with 20.0mL × 3 of ethyl acetate, the organic phases were combined, dried over anhydrous sodium sulfate, and separated by column chromatography (eluent: petroleum ether/ethyl acetate ═ 50:1) to obtain the objective 2, 11-dimethylchromeno [4,3-b ] pyrrolo [3,4-d ] pyridine-1, 3(2H,4H) -dione in 74 mg of yellow solid yield.

The product prepared in the eleventh embodiment is characterized by nuclear magnetic hydrogen spectrum and nuclear magnetic carbon spectrum, the specific spectrogram is shown in fig. 21-22, and the specific data is as follows:

¹HNMR(400MHz,CDCl₃)δ8.23(d,J＝7.8Hz,1H),7.38(t,J＝7.8Hz,1H),7.09(t,J＝7.5Hz,1H),6.97(d,J＝8.2Hz,1H),5.66(s,2H),3.15(s,3H),2.88(s,3H)；¹³C NMR(101MHz,CDCl₃)δ168.0,167.0,157.2,156.3,153.8,134.3,133.2,125.7,122.5,121.8,121.0,120.7,117.5,63.7,24.0,21.2.

example twelve

Preparation of 2, 4-dimethyl-6- (pyridin-3-yl) -1H-pyrrolo [3,4-c ] pyridine-1, 3(2H) -dione:

n- (1- (pyridin-3-yl) vinyl) acetamide (48.7mg, 0.3mmol), N-methylmaleimide (102.0mg, 0.9mmol), a promoter manganese acetate (26.5mg, 0.15mmol) were weighed out, and 2mL of a mixed solvent (DMF/PhCl ═ 1:1) was added thereto, and reacted in an oil bath at 120 ℃ for 24 hours, after completion of the reaction, the reaction product was extracted with 20.0mL × 3 of ethyl acetate, the organic phases were combined, dried over anhydrous sodium sulfate, and separated by column chromatography (eluent: petroleum ether/ethyl acetate ═ 50:1) to obtain the objective 2, 4-dimethyl-6- (pyridin-3-yl) -1H-pyrrolo [3,4-c ] pyridine-1, 3(2H) -dione in the form of 23.0mg of a white solid with a yield of 30%.

The products prepared in the twelfth embodiment are characterized by nuclear magnetic hydrogen spectrum and nuclear magnetic carbon spectrum, the specific spectrogram is shown in fig. 23-24, and the specific data are as follows:

¹H NMR(400MHz,CDCl₃)δ9.30(s,1H),8.74–8.68(m,1H),8.41(dt,J＝8.1,2.0Hz,1H),8.01(s,1H),7.44(dd,J＝8.0,4.8Hz,1H),3.20(s,3H),2.94(s,3H)；¹³C NMR(101MHz,CDCl₃)δ168.0,166.8,159.8,157.1,151.2,148.7,141.6,134.9,133.4,123.7,121.8,111.1,24.2,21.3.

EXAMPLE thirteen

Preparation of 4-methyl-6-phenyl-1H-pyrrolo [3,4-c ] pyridine-1, 3(2H) -dione:

n- (1-phenylvinyl) acetamide (48.4mg, 0.3mmol), maleimide (89.1mg, 0.9mmol), promoter manganese acetate (26.5mg, 0.15mmol) were weighed out, 2mL of a mixed solvent (DMF/PhCl ═ 1:1) was added thereto, and the mixture was reacted in an oil bath at 120 ℃ for 24 hours, after completion of the reaction, the reaction product was extracted with 20.0mL × 3 of ethyl acetate, the organic phases were combined, dried over anhydrous sodium sulfate, and separated by column chromatography (eluent: petroleum ether/ethyl acetate ═ 50:1) to obtain the target product 4-methyl-6-phenyl-1H-pyrrolo [3,4-c ] pyridine-1, 3(2H) -dione (12.1 mg, white solid, yield 17%).

And performing nuclear magnetic hydrogen spectrum and nuclear magnetic carbon spectrum characterization on the product prepared in the third embodiment, wherein specific spectrograms are shown in figures 25-26, and specific data are as follows:

¹H NMR(400MHz,DMSO-d6)δ11.54(s,1H),8.23(dd,J＝6.6,3.0Hz,2H),8.15(s,1H),7.73–7.26(m,3H),2.81(s,3H)；¹³C NMR(101MHz,DMSO-d6)δ169.3,167.7,160.9,155.6,142.4,137.2,130.5,128.9,127.4,122.1,110.9,20.8.

example fourteen

Preparation of 2-ethyl-4-methyl-6-phenyl-1H-pyrrolo [3,4-c ] pyridine-1, 3(2H) -dione:

n- (1-phenylvinyl) acetamide (48.4mg, 0.3mmol), N-ethylmaleimide (114.9mg, 0.9mmol), promoter manganese acetate (26.5mg, 0.15mmol) were weighed out, 2mL of a mixed solvent (DMF/PhCl ═ 1:1) was added thereto, and the mixture was reacted in an oil bath at 120 ℃ for 24 hours, after completion of the reaction, the reaction product was extracted with 20.0mL × 3 of ethyl acetate, the organic phases were combined, dried over anhydrous sodium sulfate, and separated by column chromatography (eluent: petroleum ether/ethyl acetate ═ 50:1) to obtain the desired product 2-ethyl-4-methyl-6-phenyl-1H-pyrrolo [3,4-c ] pyridine-1, 3(2H) -dione (49.1 mg, white solid, yield 61%).

The nuclear magnetic hydrogen spectrum and nuclear magnetic carbon spectrum characterization is carried out on the product prepared in the fourteenth embodiment, the specific spectrogram is shown in fig. 27-28, and the specific data is as follows:

¹H NMR(400MHz,CDCl₃)δ8.11–8.02(m,2H),7.94(s,1H),7.48(dd,J＝5.2,2.0Hz,3H),3.74(q,J＝7.2Hz,2H),2.92(s,3H),1.28(t,J＝7.2Hz,3H)；¹³C NMR(101MHz,CDCl₃)δ168.0,166.8,162.2,156.6,141.4,137.7,130.5,128.9,127.4,120.9,111.0,33.0,21.3,13.8.

example fifteen

Preparation of 2-cyclohexyl-4-methyl-6-phenyl-1H-pyrrolo [3,4-c ] pyridine-1, 3(2H) -dione:

n- (1-phenylvinyl) acetamide (48.4mg, 0.3mmol), N-cyclohexylmaleimide (161.3mg, 0.9mmol), a promoter manganese acetate (26.5mg, 0.15mmol) were weighed out, 2mL of a mixed solvent (DMF/PhCl ═ 1:1) was added thereto, and the mixture was reacted in an oil bath at 120 ℃ for 24 hours, after completion of the reaction, extracted with 20.0mL × 3 of ethyl acetate, the organic phases were combined, dried over anhydrous sodium sulfate, and separated by column chromatography (eluent: petroleum ether/ethyl acetate ═ 50:1) to obtain the desired product 2-cyclohexyl-4-methyl-6-phenyl-1H-pyrrolo [3,4-c ] pyridine-1, 3(2H) -dione (63.5 mg, white solid, 66% yield).

The products prepared in the fifteenth embodiment are characterized by nuclear magnetic hydrogen spectrum and nuclear magnetic carbon spectrum, the specific spectrogram is shown in fig. 29-30, and the specific data are as follows:

¹H NMR(400MHz,CDCl₃)δ8.13–8.04(m,2H),7.94(s,1H),7.54–7.43(m,3H),4.12(tq,J＝12.4,4.0Hz,1H),2.93(s,3H),2.21(qd,J＝12.5,3.4Hz,2H),1.88(dt,J＝11.4,3.1Hz,2H),1.78–1.65(m,3H),1.44–1.26(m,3H)；¹³C NMR(101MHz,CDCl₃)δ168.3,167.0,162.2,156.6,141.3,137.9,130.4,128.9,127.5,120.8,111.0,51.1,29.7,25.9,25.0,21.2.

example sixteen

Preparation of 4-methyl-2, 6-diphenyl-1H-pyrrolo [3,4-c ] pyridine-1, 3(2H) -dione:

n- (1-phenylvinyl) acetamide (48.4mg, 0.3mmol), N-phenylmaleimide (157.4mg, 0.9mmol), promoter manganese acetate (26.5mg, 0.15mmol) were weighed out, 2mL of a mixed solvent (DMF/PhCl ═ 1:1) was added thereto, and the mixture was reacted in an oil bath at 120 ℃ for 24 hours, after completion of the reaction, the reaction product was extracted with 20.0mL × 3 of ethyl acetate, the organic phases were combined, dried over anhydrous sodium sulfate, and separated by column chromatography (eluent: petroleum ether/ethyl acetate ═ 50:1) to obtain 54.0mg of the target product 4-methyl-2, 6-diphenyl-1H-pyrrolo [3,4-c ] pyridine-1, 3(2H) -dione, a white solid, with a yield of 57%.

The products prepared in the sixteen examples are characterized by nuclear magnetic hydrogen spectrum and nuclear magnetic carbon spectrum, the specific spectrogram is shown in figures 31-32, and the specific data are as follows:

¹H NMR(400MHz,CDCl₃)δ8.18–8.11(m,2H),8.08(s,1H),7.56–7.50(m,5H),7.47–7.39(m,3H),3.00(s,3H)；¹³C NMR(101MHz,CDCl₃)δ167.1,166.0,162.7,157.4,140.9,137.6,131.3,130.7,129.1,129.0,128.3,127.6,126.5,120.4,111.4,21.5.

example seventeen

Preparation of 2-benzyl-4-methyl-1H-pyrrolo [3,4-c ] pyridine-1, 3(2H) -dione:

n- (1-phenylvinyl) acetamide (48.4mg, 0.3mmol), N-benzylmaleimide (171.9mg, 0.9mmol), promoter manganese acetate (26.5mg, 0.15mmol) were weighed out, 2mL of a mixed solvent (DMF/PhCl ═ 1:1) was added thereto, and the mixture was reacted in an oil bath at 120 ℃ for 24 hours, after completion of the reaction, extracted with 20.0mL × 3 of ethyl acetate, the organic phases were combined, dried over anhydrous sodium sulfate, and separated by column chromatography (eluent: petroleum ether/ethyl acetate ═ 50:1) to obtain the desired product 2-benzyl-4-methyl-1H-pyrrolo [3,4-c ] pyridine-1, 3(2H) -dione 79.9mg, a white solid, with a yield of 81%.

The products prepared in the seventeen example are characterized by nuclear magnetic hydrogen spectrum and nuclear magnetic carbon spectrum, the specific spectrogram is shown in figures 33-34, and the specific data are as follows:

¹H NMR(400MHz,CDCl₃)δ8.12–8.03(m,2H),7.96(s,1H),7.53–7.43(m,5H),7.38–7.25(m,3H),4.85(s,2H),2.94(s,3H)；¹³C NMR(101MHz,CDCl₃)δ167.8,166.6,162.3,156.8,141.2,137.6,135.9,130.5,128.9,128.7,128.6,127.9,127.4,120.8,111.1,41.7,21.3.

EXAMPLE eighteen

Preparation of 2- (4-bromophenyl) -4-methyl-6-phenyl-1H-pyrrolo [3,4-c ] pyridine-1, 3(2H) -dione:

weighing N- (1-phenylvinyl) acetamide (48.4mg, 0.3mmol), 1- (4-bromophenyl) -1H-pyrrole-2, 5-dione (226.7mg, 0.9mmol) and promoter manganese acetate (26.5mg, 0.15mmol), adding mixed solvent 2mL (DMF/PhCl ═ 1:1), reacting in an oil bath kettle at 120 ℃ for 24 hours, extracting with 20.0mL × 3 ethyl acetate after the reaction is finished, combining organic phases, drying with anhydrous sodium sulfate, separating by column chromatography (eluent: petroleum ether/ethyl acetate ═ 50:1) to obtain the target product 2- (4-bromophenyl) -4-methyl-6-phenyl-1H-pyrrolo [3,4-c ] pyridine-1, 3(2H) -dione 58.5mg, white solid, the yield was 50%.

Performing nuclear magnetic hydrogen spectrum and nuclear magnetic carbon spectrum characterization on the product prepared in the eighteenth embodiment, wherein specific spectrograms are shown in fig. 35-36, and specific data are as follows:

¹H NMR(400MHz,CDCl₃)δ8.18–8.11(m,2H),8.08(s,1H),7.68

–7.60(m,2H),7.53(dd,J＝5.3,2.0Hz,3H),7.39–7.31(m,2H),3.00(s,3H)；¹³C NMR(101MHz,CDCl₃)δ166.8,165.7,162.9,157.6,140.8,137.5,132.3,130.8,130.4,129.1,127.9,127.6,122.1,120.3,111.5,21.6.

example nineteen

Preparation of 2- (4-iodophenyl) -4-methyl-6-phenyl-1H-pyrrolo [3,4-c ] pyridine-1, 3(2H) -dione:

n- (1-phenylvinyl) acetamide (48.4mg, 0.3mmol), 1- (4-iodophenyl) -1H-pyrrole-2, 5-dione (269.2mg, 0.9mmol), promoter manganese acetate (26.5mg, 0.15mmol) were weighed, 2mL of mixed solvent (DMF/PhCl ═ 1:1) was added, the mixture was reacted at 120 ℃ in an oil bath, after completion of the reaction, the mixture was extracted with 20.0 mL. times.3 of ethyl acetate, the organic phases were combined, dried over anhydrous sodium sulfate, and subjected to column chromatography (eluent: petroleum ether/ethyl acetate ═ 50:1) to obtain the desired product 2- (4-iodophenyl) -4-methyl-6-phenyl-1H-pyrrolo [3,4-c ] pyridine-1, 3(2H) -dione 67.3mg, a pale yellow solid, the yield was 51%.

The products prepared in the nineteenth embodiment are characterized by nuclear magnetic hydrogen spectrum and nuclear magnetic carbon spectrum, the specific spectrogram is shown in fig. 37-38, and the specific data are as follows:

¹H NMR(400MHz,CDCl₃)δ8.13(dd,J＝6.7,2.9Hz,2H),8.07(s,1H),7.84(d,J＝8.2Hz,2H),7.52(dd,J＝5.3,2.1Hz,3H),7.21(d,J＝8.2Hz,2H),2.99(s,3H)；¹³C NMR(101MHz,CDCl₃)δ166.6,165.6,162.8,157.6,140.8,138.3,137.5,131.1,130.8,129.0,128.0,127.6,120.3,111.4,93.6,21.5.

it is intended that the one or more embodiments of the present specification embrace all such alternatives, modifications and variations as fall within the broad scope of the appended claims. Therefore, any omissions, modifications, substitutions, improvements, and the like that may be made without departing from the spirit and principles of one or more embodiments of the present disclosure are intended to be included within the scope of the present disclosure.